Journal Article

SSBP1 faux pas in mitonuclear tango causes optic neuropathy

Zelinger, Lina, Swaroop, Anand

2020

Overview

Mitochondrial dysfunction or loss is evident in neurodegenerative diseases. Furthermore, mitochondrial DNA (mtDNA) mutations associated with NADH dehydrogenase subunits and nuclear gene mutations that affect mitochondrial function result in optic neuropathies. In this issue of the JCI, Del Dotto et al. and Piro-Mégy et al. identify heterozygous mutations in nuclear-encoded mitochondrial single-strand binding protein 1 (SSBP1) in patients with apparently dominant optic neuropathy with or without extraocular phenotypes. Both research groups reported similar mitochondrial findings in response to SSBP1 mutations. However, the specific SSBP1 mitochondria-associated function in retinal ganglion cells (RGCs) and the resulting optic nerve remains unclear. We suggest that high expression of SSBP1 during RGC differentiation is critical for mtDNA maintenance to produce appropriate optic nerve connectivity and that SSBP1 mutations in dominant optic atrophy patients do not permit stable binding to N6methyldeoxyadenosine on the heavy strand involved with replication, leading to disruptions of mtDNA and, eventually, optic nerve dysfunction.

• Publisher: American Society for Clinical Investigation
• Subject: Atrophy / Biomedical research / Biosynthesis / Dehydrogenases / Deoxyribonucleic acid / DNA / Genes / Genomes / Medical prognosis / Mitochondria / Mitochondrial DNA / Mutation / NADH / NADH dehydrogenase / Neural networks / Neurodegenerative diseases / Neurons / Optic atrophy / Optic nerve / Optic neuropathy / Phenotypes / Proteins / Retina / Retinal ganglion cells / RNA polymerase